Irsogladine upregulates expressions of connexin32 and connexin26 in the rat liver.

A gap junction is the channel for cell-to-cell communication and plays an important role in the maintenance of tissue homeostasis, control of cell growth and differentiation, and prevention of experimental hepatocarcino-genesis. Irsogladine, an antiulcer drug, augments gap junctional intercellular communication in gastric mucosa, but the effect of irsogladine on the liver remains uncertain. In this study the effects of irsogladine on the liver were investigated from the viewpoints of gap junctional protein connexin (Cx)32 and Cx26 in rats. Twelve rats were divided into a control group (n=6) and the irsogladine group (n=6) in which irsogladine (20 mg/kg per day) was administered orally for 3 days before sample collection, and the two groups were compared in regard to liver enzymes (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH)), serum- and tissue-calcium concentrations, immunohistochemical expressions of Cx32 and Cx26, and RT-PCR analysis. In immunohistochemistry, analyzed using an image processor for analytical pathology (IPAP), the number of Cx32-positive spots was higher and the area of Cx26-positive spots were larger in the irsogladine group than those in the control group (P=0.036 and P=0.00032, respectively). In RT-PCR analysis, the mRNA of Cx32 or Cx26 in the irsogladine group showed a tendency to be higher than in the control group, but not significantly (Cx32, P=0.70; Cx26, P=0.07). Another 30 rats were used for measurements of cyclic-adenosine monophosphate (c-AMP) of the liver. c-AMP concentration was increased 1 h after the administration of irsogladine, which partially explained how the Cxs were upregulated. These findings may suggest that irsogladine upregulates Cx32 and Cx26 expressions in the liver of rats.